Non-asthmatic obstructive pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), are among the major causes of morbidity and mortality in Western countries, and this disease is expected to increase substantially in the coming decades. The two major risk factors for COPD are cigarette smoking and occupational exposure to chemical agents and dust, and atmospheric pollution in general.
The epidemiological data indicate that a very large number of patients suffer from the disease (9.34/1000 men and 7.33/1000 women), and the financial and social burden was estimated at 23,900 million dollars in 1993 in the USA alone. The importance of COPD, not only in scientific terms but above all from the socioeconomic standpoint, is also confirmed by the institution of an international project called GOLD (Global Initiative for Chronic Obstructive Lung Disease), which is designed to make the world's population aware of the risks deriving from COPD and to reduce the morbidity and mortality it entails. The project is sponsored by a number of public and private organisations, including the NHLBI and the WHO (www.goldcopd.com).
From the diagnostic standpoint, the definition of COPD is not universally agreed (D M Mannino. Resp. Care 2003; 48: 1185-93); however, it can be defined as a disease characterised by respiratory failure which is not fully reversible and remains unchanged for several months (P K Jeffery. Thorax 1998; 53: 129-36). A characteristic feature of COPD patients is the chronic presence of coughing and catarrh, although not all patients who exhibit these symptoms later develop COPD. However, the presence of coughing and bronchial hypersecretions for numerous days a year is very often a warning sign of COPD.
The airways of COPD patients also feature a marked presence of inflammatory processes, although the predominant cell phenotypes and anatomical location are different from those found in asthma, another pulmonary disease (P K Jeffery. Thorax 1998; 53: 129-36). Although there may be a marginal overlap of the two diseases in some patients, asthma and COPD are two distinct disorders, with very different guidelines for their diagnosis and pharmacological treatment (B R Celli et al. Eur. Respir. J. 2004; 932-46; Am. Thoracic Society. Am. Rev Respir. Dis. 1991; 152: S77-S121).
These guidelines, issued jointly by the ATS (American Thoracic Society) and ERS (European Respiratory Society), give precise information about the specific characteristics of the two diseases, allowing a differentiated diagnosis (B R Celli et al. Eur. Respir. J. 2004; 932-46), which is required to treat the disease effectively.
The distinctive signs of COPD are appearance in middle age, symptoms that progress slowly, a long personal history of smoking, abundant phlegm, and frequent flare-ups of infectious origin, whereas asthma is characterised by early onset, variable symptoms, which are present during the night or in the early morning, the presence of allergies, rhinitis or eczema, a family history of the disease, and largely reversible broncho-obstruction (B R Celli et al. Eur. Respir. J. 2004; 932-46).
As stated in the ATS/ERS guidelines, the medicinal products currently available reduce the symptoms, but as expressly indicated, “At present, no treatment has modified the rate of decline in lung function. The inhaled route is preferred” (B R Celli et al. Eur. Respir. J. 2004; p. 936).
There is consequently an evident need for new drugs to treat COPD, especially drugs which can be used by inhalation. Acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs), administered by the inhalation route, are highly effective against asthma, as demonstrated by EP0499143B1.